VAGOTOMY IN HYPERTROPHIC PULMONARY OSTEOARTHROPATHY ASSOCIATED WITH BRONCHIAL CARCINOMA

343

VAGOTOMY IN HYPERTROPHIC PULMONARY OSTEOARTHROPATHY ASSOCIATED WITH BRONCHIAL CARCINOMA R. L. HUCKSTEP M.A., M.D. Cantab., F.R.C.S.E. LATE THORACIC SURGICAL HOUSE-SURGEON

P. E. BODKIN M.B. Cantab., F.F.R. REGISTRAR,

MEYERSTEIN INSTITUTE OF RADIOTHERAPY

MIDDLESEX

HOSPITAL, LONDON, W.1

SiNcE Hippocrates first described clubbing of the fingers and toes in the 5th century B.C. there have been numerous descriptions of the condition, including an important publication by Mendlowitz (1942). Some of the underlying pathological causes include pulmonary and cardiac conditions, ulcerative colitis, steatorrhoea, cirrhosis of the liver, roundworm infestation, and, rarely, thyroidectomy (Mendlowitz 1942). In some cases finger clubbing may be associated with

incapacitating hypertrophic osteoarthropathy. The most common cause of severe osteoarthropathy is bronchial carcinoma. The proportion of bronchial carcinoma reported as showing painful osteoarthropathy varies from 1-2% (Semple and McCluskie 1955) and 5-10% (Flavell 1956) up to 50% (Alvarez 1948). The incidence is probably well under 5%. It is peripheral carcinoma rather than the central tumour which is more commonly associated with osteoarthropathy. The peripheral type is a relatively uncommon form of lung carcinoma, and is often a localised lesion involving neither pleura nor hilum. It is usually surprisingly small in view of the severity of the symptoms in the limbs. Often a quite astonishing improvement takes place after pneumonectomy or even after local removal of the tumour. There is often complete loss of pain within a few hours, and the effusions in the joints may improve after a few days, The clubbing of the fingers and toes sometimes progressively improves, the nails returning to normal as the nail grows out (Flavell 1956). The satisfactory results of resection in man are also seen the dog (Lumb and Carlson 1956). Simple operations have had an equally satisfactory effect on pulmonary osteoarthropathy-e.g., ligation of the pulmonary artery on the side of the lesion (Wyburn-Mason 1948) and

Fig, I-Case 1: cedema of hands and clubbing of fingers.

denervation of the lung hilum in inoperable carcinoma (Brea 1948, Hansen 1954). In these operations division of the nerve-supply was apparently the deciding factor in relieving the joint symptoms, rather than - any direct interference with the tumour. Following these observations and his own previous results of attempted removal, Flavell (1956) denervated the hilum in two cases of inoperable carcinoma with equally satisfactory results. The effect was then tried, in three cases, of simple division of the vagus immediately above the hilum without disturbing the hilar structures; the pulmonary osteoarthropathy in all three cases subsided immediately. In view of the remarkable palliation observed by Flavell, vagotomy was done in two advanced cases of unresectable pulmonary carcinoma with severe osteoarthropathy. In one case the osteoarthropathy was so incapacitating, with both hands and feet extremely painful and swollen, that the patient was completely crippled. Case 1.-A man,

Case-reports aged 64, was admitted to hospital in May,

1956. with acivanced pulmonary osteoarthropathy. Severe nain

limited the movements of his hands,

elbows, feet,

and

knees. He was bedridden. The symptoms had started in March, 1956, a week after an attack’ of pneumonia. He had been a coalminer

previously and had been a heavy smoker. many years

On examination his general condition was poor. His hands were swollen with oedema and showed severe clubbing (fig. 1). Pain

particularly in his right hand, wrist and,

was

severe

elbow. He had massive oedema of his ankles and feet with

Fig. 2-Case 1:tomograph showing rounded mass in upper lobe of left lung.

entry was diminished over his lett upper rhonchi were heard over his left lung. He was dyspnoeic on the slightest exertion and had marked bilateral gynsecomastia. There were no other relevant findings. Radiography of his chest showed a peripheral rounded opacity in the upper lobe of the left lung. Tomography showed that this opacity was homogeneous and had rather ill-defined margins, suggesting a bronchial carcinoma (fig. 2). Bronchoscopy showed no abnormality. Severe bronchitis contra-indicated resection. Treatment.-Three days after admission, deep X-ray therapy was begun and a tumour dose of 3485r was given over thirty days. In spite of this there was no improvement in the severe pain of the osteoarthropathy, the dyspnoea was not alleviated, and the patient remained completely bedridden. Although his very poor condition made him a grave operative risk, it was thought justifiable to try the effect of vagotomy, without attempting to remove the tumour. Operation.-A left lateral thoracotomy was done in June, 1956, by Mr. J. R. Belcher. The vagus nerve was identified and divided beneath the arch of the aorta immediately below the point where the recurrent laryngeal nerve was given off. No other structures were disturbed. Postoperative course.-Within twenty-four hours all the

extreme tenderness. Air

lobe, and

numerous

344 bones and joints were relieved, the swelling and (1956). An unusual feature was the bilateral gynaecomasfia oedema of the hands and feet were regressing, and the movein case 1, which regressed after vagotomy. The association ments of the hands and fingers had much improved. In three of gynaecomastia with carcinoma of the bronchus has been days the oedema had completely disappeared, the dyspnoea noted previously; Stephens (1928) reported an incidence of was considerably improved, and the patient got up. At the 7%, and Semple and McCluskie (1955) of 83%. No case end of ten days he was walking round the ward pain-free. Discharge and follow-up.-He was discharged from hospital has hitherto been reported which had been successfully treated by vagotomy. on the thirteenth postoperative day. On the twenty-fifth Although the causation of osteoarthropathy is unknown, postoperative day he walked into the outpatients clinic without the nervous theory of Cudkowicz and Armstrong (1953; any pain, oedema, or gynaecomastia. He was last seen nine months later, when he complained of considerable loss of appears to be the soundest. They postulate a pulmonary weight and vomiting. His general condition was deteriorating, autonomic systemic vascular reflex by which ischsmia in and his liver was grossly enlarged, but he still had no pain or parts of the lung distal to the tumour reflexly cause oedema, although the clubbing was still present. He was not systemic arteriovenous anastomoses to open up in the dyspnoeic and had no gynxcomastia. limbs. Case 2.-A man, aged 57, was admitted in August, 1956, In the present two cases the following points support complaining of feeling unwell and of having lost weight since the theory that hypertrophic pulmonary " osteoarthropathy an attack of influenza " in February. Since May, 1956, he is a nervous and not a chemical due to primarily had noticed clubbing of his fingers and toes and had increasing ’ painful swelling of his ankles and knees. Mild dyspnœa had mechanism: been present for the same period. He had smoked heavily (1) If osteoarthropathy were caused by a chemical substance liberated by the tumour, one would expect that the most for forty years. severe manifestations would be associated with tumours with On examination he had marked clubbing of his fingers and extensive secondary deposits. Local removal of a small tumour, toes and swelling of his ankles and knees. Movement of these and limited. was however, may give remarkable and usually permanent relief painful joints Radaography ot his chest showed a large rounded mass m from osteoarthropathy. It is uncommon for pain and swelling to occur after resection, even though extensive metastases the right mid-zone, extending outwards to the chest wall in the axilla (fig. 3). develop later. a submucous infiltration of showed the lateral (2) The associated gynaecomastia could be explained by the Bronchoscopy wall of the right main bronchus, and biopsy of this area dispulmonary autonomic systemic vascular reflex theory, arteriovenous anastomoses opening up in the breast as in the limbs. closed a poorly differentiated carcinoma. was done in (3) Many lesions, totally different in aetiology andpathology, Operation.-A right thoracotomy August, 1956 the manifestations of hypertrophic pulmonary Mr. W. A was found the in produce J. Jackson. by growth right upper lobe, extending across the oblique fissure but not adherent to osteoarthropathy. A common autonomic pathway could be the parietal pleura. Large lymph-nodes involved by carcinoma postulated for most of these, but would meet with many difficulties by a chemical or a hormonal explanation. In the in the hilum made the growth inoperable. The vagus nerve was therefore identified above the hilum and divided. present cases simple division of the vagus produced relief of Postoperatively the relief of pain was immediate and the the pain and resolution of the cedema, although the pulmonary lesion was undisturbed. (It might be objected that the deep cedema disappeared within forty-eight hours. On the thirteenth a course of to the X-ray therapy to the primary lesion might have had an effect, postoperative day deep X-ray therapy primary tumour and to bilateral supraclavicular glands which but this is extremely unlikely because in case 2 the beneficial effects of the vagotomy were clear before the X-ray therapy had appeared since the operation, was begun. A tumour dose was started.) of 2834r was given over three weeks. The patient was disfrom on 1956. charged hospital Sept. 24, The complete relief of the pain and the disappearance Follow-up.-In January, 1957, he had a second palliative of the oedema, despite the progression of the disease and course of deep X-ray therapy to secondary deposits in his the persistence of clubbing, appear, from the follow-up pelvic bones, ribs, and cervical lymph-nodes. Despite pro- in these cases, to be permanent. gression of his metastases he had no further symptoms from Many patients with hypertrophic pulmonary osteo his pulmonary osteroarthropathy. There was no change in associated with an inoperable carcinoma of arthropathy to the degree of clubbing. His general condition continued the bronchus might receive much benefit from vagotomy deteriorate. and he died in March. 1957. Discussion (which might be done through a thoracoscope). Probably all patients undergoing thoracotomy for inBoth patients carcinoma of the bronchus, should also undergo operable had severe pulon the side of the lesion, irrespective routine vagotomy monary osteoarof whether have they osteoarthropathy at the time or nec, thropathy, of In this who have, or may have, one of the way patients which pain was the most painful manifestations of carcinoma of the bronchus prominent sympThis pain may be saved a great deal of pain and discomfort and will tom. therefore be able to spend several months of active life, over-

pains in the

completely

shadowed the pulmonary symptoms of carcinoma. The rapid and complete relief of pain in the joints, followed by reso-

Fig. 3-Case 2: radiograph showing rounded mass

in right mid-zone of chest.

lution of the swelling and oedema, confirm the finding of Flavell

Summary Two

patients with inoperable pulmonary carcinoma an: severe hypertrophic pulmonary osteoarthropathy treated by vagotomy obtained immediate complete relief of disabling pain. Associated oedema and, in one case, gynæcomastia also disappeared. The possible mechanism of hypertrophic pulmon= osteoarthropathy is discussed, and a nervous reflex favoured.

Despite the fact that this condition is rare, patients«’undergo thoracotomy for an unresectable carcinoma -

345 the bronchus should have a vagotomy on the side of the lesion done as a routine. In inoperable cases with hyper-

TABLE I-FORMS OF PENICILLIN TREATMENT

trophic pulmonary osteoarthropathy this should be done where possible. By this relatively minor operation these patients will not only be saved much pain and misery but will also possibly live many months of active life. We are grateful to Prof. B. W. Windeyer, Mr. T. Holmes Sellors, liiss M. D. Snelling, Mr. J. R. Belcher, and Dr. A. M. Jelliffe for permission to publish these cases, and we wish to thank Mr. M. and the staff of the photographic department of the Middlesex Hospital for their invaluable help with the illustrations.

Turney

REFERENCES Avarez, G. H. (1948) Rev. Asoc. med. argent. 62, 690. Brea, M. M. (1948) cited in The Year Book of General Surgery (edited E. A. Graham); p. 306. Chicago. Cudkowicz, L., Armstrong, J. B. (1953) Brit. J. Tuberc. 47, 227. Havell, G. (1956) Lancet, i, 260. Hansen, J. L. (1954) Int. Congr. Dis. Chest. Lumb, W. V., Carlson, W. D. (1956) J. Amer. vet. med. Ass. 128, 185. Mendlowitz, M. (1942) Medicine, Baltimore, 21, 269. Semple, T., McCluskie, R. A. (1955) Brit. med. J. i, 754. Stephens, B. P. (1928) unpublished thesis, Mayo Clinic Foundation. Wybtrn-Mason, R. (1948) Lancet, i, 203.

The usual concentration of penicillin was 1000 units per g., but some patients had 10,000 units per g. for treatment of streptococcal infection. Penicillin powder was made up in a lactose powder base (10,000 units per g.). 1419 new patients attended during the six-month period. Of these, 1260 were outpatients,. 135 were inpatients, and 24 were treated initially as outpatients and were admitted later. This last group has been included with the outpatients, since most of the penicillin cream was applied before admission. 436 outpatients (34%) and 68 inpatients (50%) were under 14 years of age. 1286 patients received penicillin during treatment, most of them having it locally (table i).

by

PENICILLIN SENSITIVITY IN PATIENTS WITH BURNS MARY R. DAVIES M.B. Edin. RESEARCH

Results

Reactions No anaphylactic reaction occurred. In 35 cases a rash developed. In some patients this was obviously due to a cause other than penicillin (for example, measles), but in 10 patients it was considered on clinical grounds that the rash might be a penicillin sensitivity reaction (table II). Other possible sensitising agents had been given to four of these patients-namely, plasma (3), blood (1), streptomycin (1), and a jelly of unknown composition (1). 4 of the reactions followed the systemic administration of penicillin (3 intramuscularly, 1 orally) combined with local therapy. In the majority the rash occurred twelve to sixteen days after burning; in 3 it occurred on the fourth to fifth days; and in the remaining patient on the twentysecond day a few hours after the first injection of penicillin. No rash lasted longer than four days, and in the majority it subsided within forty-eight hours. 6 of the 10 patients had penicillin cream applied again, three days to six months later, with no reaction. Only 1 patient had any systemic upset accompanying the rash.

REGISTRAR,

BURNS RESEARCH

UNIT,

MEDICAL RESEARCH COUNCIL BIRMINGHAM ACCIDENT HOSPITAL

WITHIN recent years there have been a number of deaths from penicillin therapy (Wilensky 1946, Waldbott 1949, British Medacal Journal 1951, Thompson 1952, Harpman 1952, Kern and Wimberley 1953, Feinberg and Feinberg 1956) and an increase in sensitivity reactions (Lancet 1957). The reported incidence has varied from 12% (Lepper et al. 1949) to 605% (Cornia et al. 1945), but 5-6% seems to be the usual reaction-rate following intramuscular injection (Mayer et al. 1953, Feinberg and Feinberg 1956). Detailed reports of reactions following local application of penicillin are few, but Kern and Wimberley (1953) stated that it leads to sensitivity more commonly than any other mode of administration; and figures of 10-20% have been cited (Templeton et al. 1947). By contrast, Collier (1958) found no sensitivity reactions in about 11,000 minor burns and wounds treated

with penicillin

ointment.

Penicillin cream has been used as the routine treatment for burns at the Birmingham Accident Hospital since 1945. It

was

introduced

as a

result of the observation in

This patient sustained an 8% burn of face and hands. The hands were dressed with penicillin cream and the face was treated by exposure with penicillin powder. The dressings were changed on days 1, 4, 11, and 14. On the evening of day 14 an urticarial rash developed on the legs and trunk. The patient was given mepyramine 100 mg. t.d.s., and calamine lotion was applied locally. The following day the rash continued ; she complained of abdominal pain and vomited twice. On day 16 the dressing was changed to and the rash faded. Skin-grafting was carried out on day 19 and tulle-gras dressings were continued. On day 31, group-A haemolytic streptococci were found on the hands, which were then dressed with penicillin cream 10,000 units per g. This dressing was repeated on days 32, 34, 36, 37, 39, and 40. There was no reaction to these later applications.

Glasgow that penicillin cream was efficacious against bsmolytic streptococcal infection of burns (Clark et al. 1943); and it has been proved to have considerable prophylactic value against the same organism (Jackson et al. 1951). In the past, sensitivity reactions to local penicillin in this unit have been few and transient (Bull et al. 1954); but, in view of the reported increasing incidence of sensitivity reactions, the risks involved in the continued use of local penicillin have been freshly assessed. Method All patients were reviewed who attended the burns unit for the first time between Jan. 1 and June 30, 1957. The clinical staff were informed of the intended survey and recorded any possible allergic reaction. The use of 1% cetriSiide as a cleansing agent was discontinued for the period of the review, since it can also cause sensitivity. Penicillin cream was made in the following base:

tulle-gras,

,

2 other patients had a definite allergic reaction; but as neither had received penicillin in any form the reaction could not be attributed to this cause. If the rashes have been correctly attributed, then the total incidence of penicillin reactions was 0-8% (10 out of 1286). The incidence in inpatients was. higher (3-3%) than in outpatients (0-5%). Although this could be due to more extensive application of the cream, it seems more